. 2023 Jun 10;12(12):e029849. doi: 10.1161/JAHA.123.029849

Table 2.

Ketone/Placebo With Preceding Aspirin and Without Aspirin

	Ketone/placebo with preceding aspirin				Ketone/placebo without aspirin				Ketone/placebo with preceding aspirin vs without aspirin
	Placebo (saline) (n=12)	3‐OHB (n=12)	Difference	P value	Placebo (saline) (n=16)	3‐OHB (n=16)	Difference	P value	Difference of difference	P value
Hemodynamic parameters
CO, L/min	5.1±1.5	7.4±2.0	2.3 [1.6, 2.9]	<0.01^*	4.8±0.6	6.8±1.0	2.0 [1.6–2.4]	<0.01^*	0.3 [−0.4, 0.9]	0.43
SV, mL	80±15	100±16	19 [14– 24]	<0.01^*	75±16	95±18	20 [15–24]	<0.01^*	0 [7–6]	0.90
RAP, mm Hg	5±2	5±2	0	0.83	4.4±2.7	3.7±3.0	−0.7 [−1.4, −0.02]	0.05	1 [0–1.6]	0.23
PAP, mm Hg	19±6	19±5	0 [−2, 2]	0.91	19.8±10.6	19.6±8.7	−0.2 [−2.0, 1.7]	0.80	0 [−2, 3]	0.82
PCWP, mm Hg	9±2	8±2	−1 [0–1]	0.11	10±5	9±5	−1 [−2, 0]	0.03^*	1 [−1, 2]	0.37
MAP, mm Hg	81±16	77±12	−4 [−9, 0.8]	0.09	92±13	91±10	−1 [−5, 2]	0.48	−3 [−9, 3]	0.32
SVR, WU	15±3	10±3	−5 [−6, −4]	<0.01^*	19±3	13±2	−5 [−4, −2]	<0.01^*	0 [−1, 2]	0.60
Heart rate, bpm	63±9	73±11	10 [7–13]	<0.01^*	66 ± 16	73±14	7 [4–11]	<0.01^*	3 [−2, 7]	0.21
SVO₂, %	70±7	75±5	5 [2–8]	<0.01^*	72±3	79±4	6 [5–8]	<0.01^*	−2 [− 4, 1]	0.28
Echocardiography
LVOT VTI, cm	22.4±3.8	23.3±3.9	0.9 [−1.7, 3.5]	0.46	18.1±3.5	22.1±4.3	4.0 [2.8–5.2]	<0.01^*	−3.1 [−5.6, −0.6]	<0.02^*
GLS, %	10.3±3.9	12.3±4.2	2.1 [1.2–3.0]	<0.01^*	9.7±3.2	11.7±3.6	2.0 [1.3–2.7]	<0.01^*	0.1 [−0.9, 1–1]	0.83
S′, cm/s	4.4±1.1	5.6±1.9	1.2 [0.5– 1.8]	<0.01^*	3.7±0.8	4.5±1.3	0.8 [0.3–1.3]	<0.01^*	0.4 [−0.4, 1–1]	0.32
LVEF, %	40±8.6	45±7	6 [3–9]	<0.01^*	35±7	43±9	8 [5–11]	<0.01^*	−2 [−6, 1]	0.21
LVEDV, mL	143±41	127±40	−16 [−29, 3]	0.02^*	174±48	165±47	−9 [−20, 2]	0.09	−7 [−23, 9]	0.38
LVESV, mL	97±46	72±30	−25 [−44, −6]	0.02^*	115±40	97±41	−17 [−24, 10]	<0.01^*	−8 [−25, 9]	0.35
TAPSE, cm	1.8±0.4	2.0±0.5	0.2 [0.0, 0.4]	0.07	1.9±0.5	2.1±0.5	0.2 [0.1–0.3]	<0.01^*	0.0 [−0.2, 0.2]	0.96
Substrates and hormones
3‐OHB, mM	0.4±0.4	4.4±0.9	4.1 [3.5–4.6]	<0.01^*	0.3±0.3	3.3±0.4	2.9 [2.7–3.1]	<0.01^*	1.1 [0.6–1.6]	<0.01^*
D‐3‐OHB, mM	0.1±0.1	1.7±0.6	1.6 [1.2, 1.9]	<0.01^*	NA	NA	NA	NA	–	–
Lactate, mmol/L	0.9±0.2	1.3±0.3	0.4 [0.2–0.60.0]	<0.01^*	1.1±0.5	1.5±0.7	0.4 [0.3–0.6]	<0.01^*	0.0 [−0.2, 0.2]	0.84
Glucose, mmol/L	7.6±0.6	7.7±0.8	0.0 [−0.2, 0.3]	0.72	5.7±0.7	5.7±0.6	0.0 [−0.4, 0.4]	0.99	−0.1 [−0.8, 0.3]	0.30
FFA, mmol/L	0.17±0.13	0.07±0.08	−0.10 [−0.17, − 0.03]	0.01^*	0.17±0.18	0.09±0.12	‐ 0.08 [−0.14, −0.01]	0.02^*	−0.02 [−0.12, 0.07]	0.60
Insulin, pM	225.4±95.0	236.6±135.4	11.2 [−33.7, 56.0]	0.59	175.3±72.1	183.4±48.4	8.2 [−20.4, 36.8]	0.55	53.16 [−21.8, 128.1]	0.16
Prostaglandins
PGE₂, pg/mL	126.1±137.2	78.0±27.2	−48.0 [−125.6, 29.5]	0.20	157.3±87.2	108.3±50.8	‐ 49.0 [−107.9, 9.8]	0.10	1.0 [−89.6, 91.7]	0.98
PGI₂, pg/mL	669.3±526.9	788.7±560.9	119.4 [−299.9, 538.7]	0.54	554.6±1236.7	581.4±660	26.8 [−815.4, 869.0]	0.95	92.6 [−851.5, 1036.7]	0.84
PGD₂, pg/mL	60.2±30.1	57.3±25.6	−2.8 [−10.0, 4.3]	0.40	117.7±44.9	109.4±40.1	−8.3 [−21.2, 4.6]	0.19	5.5 [−10.1, 21.0]	0.48

The data are shown as mean±SD. The measures were performed at the end of each intervention period. P values refer to paired t tests. bpm indicates beats per minute; 3‐OHB, 3‐hydroxybutyrate; CO, cardiac output; D‐3‐OHB, D‐3‐hydroxybutyrate; FFA, free fatty acids; GLS, numeric global longitudinal strain; LVEDV, left ventricular end‐diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end‐systolic volume; LVOT VTI, left ventricular outflow tract velocity time integral; MAP, mean arterial pressure; NA, not available; PAP, mean pulmonal artery pressure; PCWP, pulmonary capillary wedge pressure; PGD₂, prostaglandin D₂; PGE₂, prostaglandin E₂; PGI₂, prostaglandin I₂; RAP, right arterial pressure; S′, systolic mitral plane peak excursion velocity; SV, stroke volume; SVO₂, mixed venous saturation; SVR, systemic vascular resistance;TAPSE, tricuspid annular peak systolic excursion; and WU, Wood units.

P<0.05.